The proposed studies are concerned with the clarification of the normal metabolism of tissues that are sites of late complications in human diabetics, and the manner in which the metabolism and morphology of these tissues may be altered by insulin, hyperglycemia or insulin deficiency. The studies are restricted to experiments involving experimental animals and their surviving tissues. Newly developed preparations of isolated rabbit sciatic nerve fascicle, and of its endoneurial contents suitable for in vitro incubation experiments will be utilized to clarify the general characteristics of glucose and myoinositol metabolism in the neural components of peripheral nerve, and the manner in which they may be altered by experimental diabetes. Evidence will be sought that the alteration in structure of internodal myelin demonstrated in large sciatic nerve fibers from animals with experimental diabetes by our previous freeze-fracture electron microscopic studies is associated with a significant change in the concentrations of myoinositol containing lipids. The relationship between impaired sciatic motor nerve conduction velocity in rats with acute experimental diabetes, which can be corrected by insulin treatment or myoinositol feeding, and the recently demonstrated decrease in axoplasmic flow in these animals will be examined. The effects of acute experimental diabetes on the composite glucose metabolism and morphology of an intact rabbit aortic intima-media preparation will be studied. Efforts to develop a method to incubate aortic intima-media under circumstances in which the access of substrates to only the luminal face is feasible will be continued.